1. Technical Field of the Invention
The present invention relates to a method and arrangement for enhancing detection of different samples including at least first or second types of samples.
2. Background of the Invention
When considering a living organism, for example a human being, an animal or even a plant, a basic subunit of such organisms is a cell. One way to categorize such cells is by the functions they are aimed to perform in an organism; e.g.: epithelial cells, (skin) muscle cells, neural cells and the like. All these cells communicate with the surrounding world via complex mechanisms, which usually involve many different complex molecules called proteins, some of which are embedded into a cell wall. Cells live and die very much like the whole organism; they also grow, divide, and the like. In all these functions, many different parts/components of a given cell take part. These components can be proteins, enzymes (acting as catalysts for certain reactions occurring in the cell) as well as DNAs, RNAs, tRNAs, and the like. Thus, there exists an enormous number of processes (mutations) occurring in an organism per unit time, and also in each cell of the organism. Some of these mutations are important for the cell-well being, but others are dangerous, for instance, cancerous mutations.
Therefore it is very important to be able to foresee, at least partly, the behavior of a cell, to map out the reactions that occur, and their products (usually creation of new cells DNAs and/or proteins). It is equally important to be able to cure maligneous events in the body, which can arise by either invasion of other organisms (viruses or bacteria), or by processes caused within the body itself (autoimmune reactions), or by outside environmental factors such as stress.
In all of these processes, the number of out coming events is immense. Take for example, DNA strands. There are millions upon millions of different DNAs that contribute to production of even larger numbers of proteins whose function and chemistry is far more complex than that of the DNAs themselves.
It would take many lifetimes to establish the structure of even a few thousands of the DNA molecules, not to mention the proteins and/or their functions, or related drugs. Therefore, one needs fast techniques that enable the acquisition of information in parallel, and effective means of storage and handling of such information.
During the past decades, a search to develop such methods has been started. The common name for such techniques has been coined as high throughput screening (HTS). The idea is to prepare, in parallel, fewer samples so as not to use large amounts of expensive and rare chemicals but, to make as many as are feasible, as is possible. The easiest and the most logical (from the information handling point of view) way is to arrange such complex samples in a matrix. Taken from the semiconductor industry, these matrices are often referred to as “chips”.
One example of such preparation is given in FIG. 1, Biophotonics, January/February 2000, Univ. of Wisconsin, Franco Cerrina, et al. According to this technique, a matrix is created by burning away deposits from certain selected places on a chip, while depositing additional chemicals on other places. This method, although fairly fast and cheap, produces a permanent pattern on a matrix which will be used up after a single experiment. Thus, each new experiment requires production of a new matrix.
The number of elements (spots) in a matrix varies depending on the preparation method, but usually does not exceed 10,000; although, matrices as large as including 1,000,000 sites have been reported. The outcome of each single “experiment,” therefore, gives at best 10,000 results. In reality this number is much lower (around 20% of best results) due to the very poor quality of even the best matrices produced to date.
Apart from the preparation mentioned above, a complete HTS-system also has to include means of detecting for the events taking place in each spot, as well as data transfer and evaluation.
FR 2,781,886 concerns fabrication of a microsystem with multiple points for chemical or biological analysis consisting of a structure provided with micro-cups. Each micro-cup is designed to receive a reagent coupled with a conductor polymer. Each micro-cup has a receiving electrode whereon, is fixed, the reagent via of the polymer conductor, with which it is coupled. Each micro-cup also has a counter-electrode arranged so as to apply, in a volume of the micro-cup, an electric field between its counter-electrode and its receiving electrode. The structure has means for simultaneously connecting all the receiving electrodes to a first electric potential and means for simultaneously connecting all the counter-electrodes to a second electric potential for generating the electric field.
U.S. Pat. No. 5,874,219 discloses methods for concurrently processing multiple biological chip assays by providing a biological chip plate comprising a plurality of test wells, each test well having a biological chip having a molecular probe array. Samples are introduced into the test wells; subjecting the biological chip plate to manipulation by a fluid handling device that automatically performs steps to carry out reactions between target molecules in the samples and probes. The biological chip plate is subjected to a biological chip plate reader that interrogates the probe arrays to detect any reactions between target molecules and probes.
The International Application No. WO 00/54882 provides electromagnetic chips and electromagnetic biochips having arrays of individually addressable micro-electromagnetic units, as well as methods of utilizing these chips for directed manipulation of micro-particles and microstructures such as biomolecules and chemical reagents. An electromagnetic biochip includes an individually addressable micro-electromagnetic unit chip with ligand molecules immobilized on its surface. By controlling the electromagnetic field at each unit of the array and combining this control with magnetic modification of biomolecules, these chips can be used for directed manipulation, synthesis and release of biomolecules in order to increase sensitivity of biochemical or chemical analysis and reduce assay time. Other advantages with these chips include minimized damages to biological molecules and increased reproducibility of assay results. According to this invention, magnetic forces are used to control and manipulate magnetically modified molecules and particles and to promote molecular interactions and/or reactions on the surface of the chip. However, the drawback is that the detection is not sensitive, as other molecules will also be detected.